Team:NCTU Formosa/more details
Description of targeted drug
Bevacizumab(Avastin® anti-VEGF)
-A recombinant humanized monoclonal antibody drug.
-The first FDA approved therapy designed for angiogenesis inhibition.
-Direct against the vascular endothelial growth factor (VEGF).
Mechanism of drug:
Bevacizumab binds to VEGF extracellularly and inhibits VEGF from binding with VEGF receptor on vascular. By this inhibition, the uncontrollable growth of blood vessels around cancer cells can be prevented. Without the great supplement of nutrients from blood vessels, the rate of cancer cells growth will decrese. Finally, the cancer cell will shrink as the lack of nutrients[1][2][3].
[1]http://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=43234
[2] http://www.avastin-hcp.com/about-avastin/proposed-moa
[3] http://dict.youdao.com/search?le=eng&q=cheap%E3%80%81&keyfrom=dict.top
Cetuximab (Erbitux® anti-EGFR)
-A recombinant chimeric monoclonal antibody.
-directed against the epidermal growth factor (EGFR).
Mechanism of drug:
Cetuximab binds to the extracellular domain of the EGFR on cancer cells can help prevent the dimerization of the receptors. The inhibition of dimerization can prevent the further intracellular signal transduction and proliferation of cancer cells[1].
[1]http://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=42384
Trastuzumab (Herceptin® anti-HER2)
-A recombinant humanized monoclonal antibody.
-Direct against the human epidermal growth factor receptor 2 (HER2)[2][3].
Mechanism of drug:
The binding of Herceptin with extracellular domains of HER2 on cancer cells can prevent the dimerization of HER2 with other HER family member, for example HER1, HER3 and HER4 which cause further intracellular signaling transmission and cell proliferation.
Besides, by binding with HER2, the cancer cells will be flagged for destruction by the immune system which known as antibody-dependent cell-mediated cytotoxicity.
Moreover, the binding between Trastuzumab with HER2 can help prevent the shading of HER2 from cancer cell surfaces[1].
[1]http://www.herceptin.com/hcp/treatment/moa
[2]http://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=42265
[3]https://ncit.nci.nih.gov/ncitbrowser/pages/concept_details.jsf?dictionary=NCI_Thesaurus&version=15.07d&code=C1647&ns=null&type=properties&key=null&b=1&n=0&vse=null
Human practice
Skype meetup
We had 4 engaging internet discussions with teams that were KAIT_ Japan, Amoy_ China, TU Delft, and Oxford. We always learned so much from each team’s amazing idea. After exchanging ideas, we were amazed by them and what’s more, as we talked to different people from different culture, culture shock and multicultural interaction experience were something we were excited about. With all these cross-cultural meet ups, our lives had been spiced up.
Skype meeting with Amoy on May 13
Skype meeting with KAIT_Japan on May 20
Skype meeting with TU_Delft on August 4
Mini Conference with Mingdao & HSNU
We also held mini conference in Taiwan with Mindao and HSNU and CGU on June 8 to help them with their project about modeling and show how our team work on June 7th .We have organize a one day mini conference. At first, we have presentation time to every group. After presentation, we also have Q&A time to give some pieces advice also assist them to have a better experimental design and any confronted problem.
We also teach them basic experimental skills, for example, ligation and digestion.
At the end, we had vigorous discussions with as many as possible people. Now, each team have better understanding about synthetic biology and their project.
Mini conference with Mindao and HSNU on June 8
Mini Conference with Professors and iGEMers
June 14
The first-recruited team CGU come for exchanging ideas about their project. Out of excitement, it just happened to be that our projects were also about improving medical problem. We were surprised that we were helpful to each other in this conference-*. Besides, we also give them some pieces advice to manage their new team to promote their working efficiency.
Mini conference with CGU on June 14
July 3
It was a very excited day as there was a meetup with iGEMers from New Zealand Auckland IGEM team and South China University of Technology in NCTU. The main focus point on this meetup was to share and discuss the experiences of forming the iGEM teams. To make this discussion effective, our team previous leader also joined the meetup and so can provided more information with our friends. We discussed about the ways of recruiting and training members. After knowing the experiences of each other, those experiences can be a useful references for us in the future. Our instructor, Professor Chen also shared his experiences and thought about iGEM. We appreciate their coming!
Mini conference with iGEMers from New Zealand Auckland IGEM team and South China University of Technology on July 3
July 30
Professor Westenberg from Missouri University of Science and Technology came to NCTU. He gave us some valuable advice on how we can alter our experiment. We had a really great time-sharing each other's project, and show him around our campus.
Mini conference with Professor Westenberg on July 30
Biocamp
Wednesday, July 8th
In the summer, our department held a Biocamp for senior high students. Most of our team members participated in holding the event. The purpose of Biocamp is to let high school students learn about biology and have fun during the process. Three of our teammates designed a lecture to teach them synthetic biology with simple concept. What’s more, we promoted iGEM to them with introducing different iGEM projects, and conveying the essence and values of iGEM that we have realized during the processes. At last we also share our project with them specifically, the main idea of our biobricks and goals. After the lecture, we received some great response from them. All of them were fascinated by the idea of using enzymes and different assemblies of biobricks to create new functions, and interested in participating in iGEM. Hope all of them have the opportunity to become an iGEMer, enjoying the processes just like us
Doctors visit
Thursday, July 16th
An oncologist visited our university, we grasped the opportunity and we talked to the doctor and elaborated our project. We were wondering how we will help patients with our project and if we really provide a better way to prediagnose. After a long discussion about the practical use of our project and the advantages. The doctors aid he was pretty amazed by our intelligent idea that we just use ecoli to prediagnose. That simplified the procedure and rose the efficiency. We were so excited that our project could also be applied well in practical use. It could really help people!
1. Can the antigen concentration of after treatment of targeted drug be detected by serum?
Ans: Yes, not only serum test but also through biopsy.
2. In our project, we use the antibodies directly from targeted drug, is there anyone else who use the same method?
Ans: Yes, people have been using antibodies directly from targeted drug to test if the patient is suitable for this kind of therapy. That’s why the department of pathology not only uses biopsy but also detects all kinds of markers before using targeted drug therapy.
3. Has anyone tested EGFR, VEGF and HER2 markers?
Ans: Yes, these 3 markers are all detectable through serum test and biopsy.
4. Is Elisa use in hospitals?
Ans: Yes, the elisa technology has become more and more mature. It’s accuracy is higher and the quantization of the result is also improving.
5. Which part of cancer therapy is Elisa used?
Ans: Elisa is used before and after treatment.
6. Besides of IHC and FISH, are there other detection methods before breast cancer treatment?
Ans: There’s a lot of other methods, but IHC and FISH is the two most common methods.
7. Is there an unclear detection limits when using cell staining technology?
Ans: Of course there is, but currently the staining chemical agents and detection equipment are both improving, so the detection limits are decreasing.
8. What is the purpose of serum test?
Ans: In clinical pathology, serum test can be used both before and after cancer therapy. It doesn’t have to be a specific kind of cancer to be serum tested. For example, how do we determine whether the cancer has reoccurred after cancer treatment, we observe if the cancer has grown in the cancer image. Using CA125, which has an 85 percent correct rate, if the result rises there must be a chance of the cancer reoccurring.
9. Can our product make practical contribution to the medical field?
Ans: It’s a great product. Pre-detection of targeted therapy is very important. Your product provides another method of pre-detection and it can quantize the result. Currently Elisa has problems to quantize its result. Therefore if your product can prove that the antigen concentration in blood is positive correlation with the antigen on the cancer, then it would have great success.
10. How long does it take for the result of Elisa to turn out in hospitals?
Ans: Since Elisa already has a Standard Operation Procedure, so once the hospital personnel get the sample ready, the rest is left to automatic machines. The result will turn our in a few hours.
11. Is the marker tested in every hospital different?
Ans: All the hospitals follow the cancer organization’s rules, so every cancer has an opposing marker. Every procedure is standardized.
12. Does the doctor decide the dose of targeted drug?
Ans: The dose of targeted drug is related to the patient’s weight.
13. How is the accumulation of medical records systematically used to help improve cancer therapy determination?
Ans: Cancer therapy statistics are divided into stages to help improve cancer treatment. For example, the five-year survival rate of first stage cancer is accumulated. Then the five-year survival rate of second stage cancer is accumulated. The individual difference of patients is not considered in the statistics.
14. If e.coli were handed alive to the hospital, would the hospital hesitate to use it?
Ans: No, live e.colis doesn’t cause big problems.
15. If cancer is detected, is targeted drug used first or cancer surgery?
Ans: Cancer surgery is conducted first. Cancer surgeries will try to reduce the tumor to less than 1 centimeter in diameter. The purpose of targeted therapy is to kill off the rest of the cancer cells.
NCTU Asia iGEM Meetup
The big event that NCTU_FORMOSA had been preparing for so long started on 8/19, which lasted for 4 days. We had 27 teams present, about 210 attendees from China, Hong Kong and Taiwan. We even have teams from India and Kazakhstan join us during the meetup through the internet. So all the process of Asian conference is open to the whole world. Throughout the 4-day conference, each team had prepared presentation for their amazing projects and ideas. We learned about each team’s idea and the progress of their project so After all the presentations, our professors also as judges will give pieces of advice to the teams. Afterwards, Q&A time was a chance to interact with each team. Besides presentation, poster time during every meal not only fed us with exquisitely prepared food but also knowledge. All these activities enable us to rethink our project with different angles, improving our 27 projects into a new level. At the end of the conference, each team were given special gifts, embraceD bunch of friends, and feel happy and proud to be igemers. After the conference, we planned a day trip in Taipei, visiting National Palace Museum and Taipei 101. Both are the must-go attraction that nobody would miss when coming to Taiwan.
Visit in Mackay Memorial Hospital
We paid a visit to Mackay Memorial Hospital to ask some questions about prediagnosis and prescription for designing our project. And we had been educated to a certain degree that our design will function in practical use.
Following is our record.
1.We learned that before using targeted therapies we must do pre-diagnosis.
Nowadays, the most commonly used methods are IHC (immunohistorychenistry) and FISH(fluorescence in situ hybridization).
And we learned that currently there are no cancer detecting methods using blood.
Because of this, we come to realize the significance of pre-diagnosis, and that the project which we are doing will benefit the society.
2. We learned that there are several kinds of targeted drugs to fight against cancer, such as Tykerb,Herceptin ,which have different pathways to inhibit the tumor cells.Because of this, we get a first glimpse of targeted drugs and their mechanisms.
3.We learned that there are some tests to check whether the targeted therapies work or not, and whether the patients get better or not.The tests are Mammography and Positron Emission Tomography.By this experience, we know that our project can play an important role in checking whether the targeted therapies work or not, and whether the patients get better or not.
4.We learned that doctors must follow the NCCN Guideline to diagnose.
Interview with recovered patient
One gorgeous day, three of us visited a teacher, who has recovered from breast cancer for 4 years. The purpose of this meetup was to recognize deeply how a cancer patient suffered from cancer. She surprised us with her open-minded, optimistic and brave personality. She discovered the tumor by herself and confronted with her misfortune straightly. Because of her characteristic, she overcame the cancer with only 4 chemotherapies. We really appreciate her sharing.
During the conversation, we had a wonderful interaction with her, introducing our ideas and goals to her. Despite that the therapy she took was not relative to our project, we still received a lot of supportive response for our project from her. Last but not the least, we all realized some valuable experiences and feelings in the recesses of our mind from this meetup!
Interview with recovered patient on August 12
Newsletter
We took part in Amoy newsletters no 1, no2 and no3.We have shown how our team works. The best thing is that we shared our experiences to harmonize with each team member, hoping to share the key to success. We also wrote about the ethics topic that happened in Guangzhou’s Sun Yat-sen University about modifying human embryos. Lastly, we also talked about the progressing project. We had been proud and happy to share all our knowledge, our opinions and with the world.
http://issuu.com/amoy-igem/docs/2015newsletterno1?e=17843433%2F13214508
http://issuu.com/amoy-igem/docs/2015newsletterno2
http://issuu.com/amoy-igem/docs/2015newsletter-3
Achievement and Value
What have we done?
In the project
◆We created the fluorescent E.Cotectors with the single chain variable fragment (scFv) of monoclonal antibody used on targeted therapies on its outer membrane.
◆We created our E.Cotectors with the gold binding peptide (GBP) on its outer membrane.
◆We created the different colors of fluorescent E.Cotectors with different scFv of monoclonal antibodies.
◆We proved that the scFv have binding specificity and our E.Cotectors can bind to antigens to distinguish antigens overexpressed in cells.
◆We proved that our E.Cotectors can apply on different techniques of cell staining.
◆We proved that the GBP can let our E.Cotectors adhere to the gold surface.
◆We combined the Quartz crystal microbalance (QCM) technique with our E.Cotectors to measure the concentration of antigens.
More than the project
◆We constructed 25 biobricks and conducted a series of experiments to verify their functions.
◆We constructed the models to calculate the optimized environment for the highest binding affinity.
◆We designed the mechanism to guarantee the safety on the gene level and the microorganism level.
◆We promoted the communication and the cooperation among various professional fields such as synthetic biology, measurement technology, immunology, and medical science via the participation in iGEM and the accomplishment of the project.
Value on the measurement technology
◆Simultaneously detected the multiple antigens.
◆Enlarged the signal of targeted antigens.
◆Combined the antigen measurement technique with others technique, enhanced the precision, and expanded its application.
◆Enhanced the process yield in immobilization of antibodies on the medium gold surface.
◆The cost of using our E.cotectors is lower than using monoclonal antibodies targeted drugs directly on measuring antigens.
◆Value on medical diagnosis
◆Offer a new way to let doctors have more selections to make diagnosis.
◆Directly used the antibody fragment of monoclonal antibody used on targeted therapy to distinguish antigens overexpressed in cells. Provided prescription of combination, personalized, and effective targeted drugs.
Prepared for the new era of medical digitalization.
Judging Criteria
Gold medal
◆ Expand on your silver medal Human Practices activity by demonstrating how you have integrated the investigated issues into the design and/or execution of your project.
◆Improve the function of an existing BioBrick Part or Device, enter this information in the registry.
◆Help any registered iGEM team from a high-school, different track, another university, or institution in a significant way by.
Silver medal
◆Experimentally validated our parts
◆Demonstrate how your team has identified, investigated and addressed one or more of these issues in the context of your project.
◆Submitted new standard biobrick parts to the iGEM Parts Registry
◆Our project may have implications for the environment, security, safety and ethics and/or ownership and sharing. Describe one or more ways in which these or other broader implications have been taken into consideration in the design and execution of your project.
Bronze medal
◆Registered the team, had a great summer, and planned to have fun at the Jamboree.
◆Completed and submitted the Judging form.
◆A Team Wiki was designed and constructed to share a description of our project.
◆Plan to present a Poster and talk at the iGEM Jamboree.
◆Attributed all work to the proper persons.
◆Submitted at least one new standard biobrick part to the registry.